Case Of Moyamoya Disease Research Articles

Moyamoya Disease: A Review of Current Literature.

Moyamoya disease (MMD) is an infrequent disease of cerebral vasculature characterized by long-standing and progressive occlusion of large intracranial arteries. It is seen predominantly in the East Asian population. Most of the cases of MMD are sporadic, but there is a small percentage that is familial. The mode of inheritance is reported to be autosomal dominant with incomplete penetrance. Studies show that the susceptibility gene of MMD is located on chromosome 17. The clinical presentation is variable and is influenced by the age and geographic region of the patient. Children mainly present with ischemia-related neurologic episodes whereas MMD in adults can manifest as either an ischemic event or an intracranial hemorrhage (ICH). The gold standard investigation for diagnosis is cerebral angiography which reveals a smoky appearance of arteries at the base of the skull, thus granting the disease its name. The treatment is mostly surgical and includes direct and indirect revascularization procedures, which prevent the recurrence of both ischemic and hemorrhagic strokes. However, combination revascularization procedures are now on the rise due to studies showing better long-term outcomes. The aim of the article is to critically analyze the current literature and updates on various aspects of MMD including, but not limited to, etiology, diagnosis, and treatment.

Moyamoya disease with hemorrhagic stroke in a Nepalese woman

The authors report a case of Moyamoya disease in a middle aged Nepali female. Though the disease is common in other parts of Asia only one case has been reported previously from Nepal. It should be suspected as a rare cause for spontaneous intracerebral hemorrhage in adults.

Luminal and Wall Changes in Intracranial Arterial Lesions for Predicting Stroke Occurrence.

Luminal imaging (degree of stenosis) currently serves as the gold standard to predict stroke recurrence and guide therapeutic strategies in patients with intracranial large artery diseases (ILADs). We comparatively evaluated the importance of vessel wall and luminal changes in predicting stroke occurrence. Consecutive patients with ILAD in the proximal middle cerebral artery or distal internal carotid artery without proximal sources of embolism from the carotid and heart underwent time-of-flight magnetic resonance angiography, high-resolution magnetic resonance imaging, and the ring finger protein 213 (RNF213) gene variant test. Patients were followed up for >3 months. Of the 675 patients, 241 (35.7%) had atherosclerotic ILAD and 434 (64.3%) showed nonatherosclerotic ILAD (315 [46.7%] moyamoya disease cases and 119 [17.6%] dissection cases). The RNF213 variant was detected in 74.9%, 33.6%, and 3.4% patients with moyamoya disease, atherosclerosis, and dissection, respectively. Three hundred (44.4%) patients had asymptomatic ILAD, whereas 375 (55.6%) patients had symptomatic ILAD. Multivariate analysis showed that vessel enhancement and etiological subtypes, not degree of stenosis, determined by high-resolution magnetic resonance imaging and RNF213 gene variant analysis were independently associated with symptomatic ILAD. The presence of the RNF213 variant was also independently associated with recurrent cerebrovascular events. This study demonstrates the prevalence of nonatherosclerotic ILAD in East Asian patients with ILAD. Unlike luminal changes, wall changes determined by high-resolution magnetic resonance imaging and presence of the RNF213 variant could predict stroke occurrence in patients with ILADs.

Cardiac manifestations in a western moyamoya disease population: a single-center descriptive study and review.

An embryological association between moyamoya disease (MMD) and cardiac manifestations has been proposed. Data up to this point remains anecdotal, and the prevalence of cardiac manifestations in a western MMD population is uncertain. The objective of this study was to determine the prevalence of cardiac manifestations including coronary artery disease (CAD) and congenital cardiac defects in a mostly Caucasian population of MMD patients and review prior reports of such cases. Medical records of MMD patients who presented to our institution between 1990 and 2019 were retrospectively reviewed for the presence of various congenital cardiac malformations and concomitant CAD. The prevalence of congenital cardiac defects and CAD was determined. A literature search for prior cases of MMD with concomitant cardiac manifestations was performed. A total of 181 MMD patients were included in our analysis, 139 (76.8%) of whom were Caucasian. Ten patients had cardiac manifestations (5.5%). There were six total MMD patients with congenital cardiac defects (3.3%). All patients with congenital defects were diagnosed in childhood. The prevalence of congenital defects in MMD was slightly higher than the general population as reported previously (0.8-1.2%). Four MMD patients had CAD (2.2%). The mean age of patients with CAD was 41.0years (SD = 12.3, range = 33-59) in our series and 33.1years (SD = 15.0) in a review of prior reports. These mean ages of CAD are in contrast to the7th and 8th decades of lifein the general populationas indicated by prior studies. Our findings support an association between MMD and cardiac manifestations. Further investigation is warranted in order to further characterize this potential relationship and shed light on a possible cardio-cephalic neural crest syndrome.

Association of Genetic Variants With Moyamoya Disease in 13 000 Individuals: A Meta-Analysis.

Background and Purpose- A growing body of evidence indicates genetic components play critical roles in moyamoya disease (MMD). Firm conclusions from studies of this disease have been stymied by small sample sizes and a lack of replicative results. This meta-analysis was conducted to determine whether these genetic polymorphisms are associated with MMD. Methods- PubMed, Google Scholar, Embase, Wanfang, Web of Science, and China National Knowledge Infrastructure databases were used to identify potentially relevant studies published until January 2020. The Review Manager 5.2 and Stata 15.0 software programs were used to perform the statistical analysis. Heterogeneity was assessed using the Cochran Q test and quantified using the I2 test. Results- Four thousand seven hundred eleven MMD cases and 8704 controls in 24 studies were included, evaluating 7 polymorphisms in 6 genes. The fixed-effect odds ratios (95% CI) in allelic model of MMP-2 rs243865 were 0.60 (0.41-0.88) (P=0.008). In the country-based subgroup analysis, the fixed-effect odds ratios (95% CI) of RNF213 rs112735431 in allelic model were China, 39.74 (26.63-59.31), Japan, 74.65 (42.79-130.24) and Korea, 50.04 (28.83-86.88; all P<0.00001). In the sensitivity analysis, the fixed-effect odds ratios (95% CI) of allelic and dominant models were the RNF213 rs148731719 variant, 2.17 (1.36-3.48; P=0.001), 2.20 (1.35-3.61; P=0.002), the TIMP-2 rs8179090 variant, 0.33 (0.25-0.43; P<0.00001), 0.88 (0.65-1.21; P=0.440) and the MMP-3 rs3025058 variant, 0.61 (0.47-0.79; P=0.0002), 0.55 (0.41-0.75; P=0.0001), respectively. Conclusions- RNF213 rs112735431 and rs148731719 were positively, and TIMP-2 rs8179090, MMP-2 rs243865, and MMP-3 rs3025058 were inversely associated with MMD using multiple pathophysiologic pathways. Studies in larger population should be conducted to clarify whether and how these variants are associated with MMD.

PHACTR1 is associated with disease progression in Chinese Moyamoya disease.

Moyamoya disease (MMD) is a progressive stenosis at the terminal portion of internal carotid artery and frequently occurs in East Asian countries. The etiology of MMD is still largely unknown. We performed a case-control design with whole-exome sequencing analysis on 31 sporadic MMD patients and 10 normal controls with matched age and gender. Patients clinically diagnosed with MMD was determined by digital subtraction angiography (DSA). Twelve predisposing mutations on seven genes associated with the sporadic MMD patients of Chinese ancestry (CCER2, HLA-DRB1, NSD-1, PDGFRB, PHACTR1, POGLUT1, and RNF213) were identified, of which eight single nucleotide variants (SNVs) were deleterious with CADD PHRED scaled score > 15. Sanger sequencing of nine cases with disease progression and 22 stable MMD cases validated that SNV (c.13185159G>T, p.V265L) on PHACTR1 was highly associated with the disease progression of MMD. Finally, we knocked down the expression of PHACTR1 by transfection with siRNA and measured the cell survival of human coronary artery endothelial cell (HCAEC) cells. PHACTR1 silence reduced the cell survival of HCAEC cells under serum starvation cultural condition. Together, these data identify novel predisposing mutations associated with MMD and reveal a requirement for PHACTR1 in mediating cell survival of endothelial cells.

Abstract 53: Missense Pathogenic Variants in ANO1 Predispose to Moyamoya Disease

Introduction: Moyamoya disease (MMD) is a cerebrovascular disease often causing pediatric onset strokes and characterized by progressive bilateral occlusion of the distal internal carotid arteries and formation of a compensatory network of collateral vessels. Several genes harbor variants that increase the risk for MMD, but the majority of cases of European descent does not have an identified genetic cause. Hypothesis: MMD is associated with significant genetic heterogeneity, i.e., many genes in the human genome can be altered to predispose to this condition. Methods: To identify novel genes for MMD, exome sequencing was performed on DNA from 145 individuals from 80 families with one or more affected members. Bioinformatics filtering included a CADD (GRCh37-v1.4) score &gt; 20 and a minor allele frequency &lt; 0.0001 in gnomAD (v2.1.1 controls). For a subset of ANO1 mutant alleles, we characterized the channel activities via patch recording and assessed protein localization in heterologous cell cultures. Results: We identified 6 rare variants in ANO1 ( TMEM16A ), which encodes an evolutionarily conserved calcium-activated chloride channel. One rare heterozygous variant, p.Met658Val (CADD: 22.9, absent in gnomAD), was found in two very distantly related MMD families and segregated with disease in multiple affected members; p.Glu459Lys and p.Arg890Gln were identified in two unrelated affected probands. Through Matchmaker Exchange (MyGene2) collaboration, we identified 3 additional rare variants: homozygous p.Glu170Lys in a consanguineous MMD family, heterozygous p.Thr740Ile in a MMD case and p.Ala333Ser in a case with ischemic stroke. Functional analyses determined that p.Glu170Lys affects channel gating and calcium sensitivity, producing much smaller chloride current, but the channel itself is more sensitive to calcium, which means it is more likely to open. Ano1 knock out (KO) in mice is lethal by 1 week of age with pathology in multiple organ systems. Smooth muscle cells-specific KO is not lethal, and phenotyping of these mice is ongoing. Conclusions: ANO1 is a novel gene predisposing to MMD and future studies will focus on defining the role of ANO1 protein to connect the altered gene to the occlusive lesions observed in MMD patients.

High-resolution combined arterial spin labeling MR for identifying cerebral arterial stenosis induced by moyamoya disease or atherosclerosis.

Distinguishing moyamoya disease (MMD) from intracranial atherosclerotic stenosis (IAS) is critical for its treatment and outcome evaluation. This study aimed to use the combined sequences of high-resolution magnetic resonance imaging (HRMRI) and arterial spin labeling MR (ASL-MR) to identify the two entities accurately. This prospective study enrolled 58 patients with middle cerebral artery (MCA) steno-occlusion identified by digital subtraction angiography (DSA), including 27 cases of MMD and 31 cases of IAS. All patients underwent MRA, HRMRI and ASL-MR prior to DSA. Two radiologists blinded to DSA results analyzed the MR images. The inner and outer diameters of the target arteries, the wall thickness of the stenotic segment, and the perfusion status in the territories of the target arteries [cerebral blood flow (CBF), cerebral blood volume (CBV) and arterial transit time (ATT)] were measured quantitatively. The differences between MMD and IAS regarding the aspects of HRMRI and Pseudo-continuous ASLMR (PCASL-MR) maps were analyzed based on both visual characteristics and data information. Regarding the HRMRI images, MMD tended to have homogeneous and concentric vessel-wall thickening as well as collaterals adjacent to the stenotic vessels; while IAS showed eccentric and heterogeneous vessel-wall thickening. For the CBF maps of PCASL-MR, abnormal hyper-perfused spots embedded inside the hypo-perfused regions were observed in MMD instead of IAS. Quantitative analysis revealed that MMD displayed smaller inner and outer diameters, and smaller maximum wall thickness, higher average value of CBF, CBV and ATT, and higher maximum value of CBF and CBV, when compared to IAS (all P<0.01). The average wall thickness and the maximum value of ATT showed no significant difference between MMD and IAS (P>0.01). HRMRI combined with PCASL-MR may help distinguish MMD and IAS induced cerebral arterial stenosis and cerebral perfusion disorder accurately and non-invasively.

Moyamoya disease: A retrospective study of 198 cases

BackgroundMoyamoya disease belongs to rare diseases which are arousing public awareness of its importance in China. In order to investigate the clinical features of inpatients diagnosed Moyamoya disease, the study was conducted to collect clinical information data of subjects on demographic information and clinical characteristics in Henan, China. MethodsThe data of 198 cases of Moyamoya disease from 56 tertiary hospitals in Henan province from January 2003 to June 2015 were collected retrospectively. Analysis was performed based on demographic, clinical and radiological characteristics of the patients. ResultsThe mean onset age was 44.03±14.45 years old. Unilateral limb weakness (36.4%) was the most common physical examination. Primary clinical manifestation was headache and dizziness (50.3%). Cranial CT showed cerebral infarction was mainly located in the frontal lobe (27.4%). MRA and DSA showed lesions mainly located in the middle cerebral artery (30.3% and 18.7%). ConclusionsClinical manifestations of Moyamoya disease varied. Early diagnosis was necessary to reduce the misdiagnosis rate of this disease. Symptoms, radiological characteristics, and lesion localization characteristics should be fully considered, especially for indicators with a certain onset age, headache and dizziness, lesion located in the frontal lobe of middle cerebral artery.

Postoperative hemorrhage during the acute phase after direct or combined revascularization for moyamoya disease: risk factors, prognosis, and literature review.

Postoperative hemorrhage during the acute phase is rarely observed after revascularization surgery for moyamoya disease (MMD) but can have severe complications. Its risk factors and outcomes are still unclear. The aim of this study was to investigate the predictors of postoperative hemorrhage during the acute phase in MMD and examine the outcomes of the hemorrhage. The authors reviewed the preoperative clinical characteristics and radiographic features of 465 consecutive MMD cases (518 procedures) that had undergone direct or combined bypass surgery at their institution between 2009 and 2015. Patients with postoperative intracerebral hemorrhage (ICH) or ICH plus intraventricular hemorrhage (IVH) during the acute phase were screened, and then the incidence, location, and risk factors of hemorrhage in these patients were analyzed. Short-term and long-term outcomes (modified Rankin Scale scores) for these patients were also collected. Outcomes were compared between patients with and those without postoperative ICH using propensity score analysis to reduce the between-group differences in baseline characteristics. Postoperative hemorrhage occurred in 11 (2.1%; ICH = 9, IVH = 2) of 518 procedures (mean patient age 39.82 ± 8.8 years). Hemorrhage occurred in the first 24 hours after the operation in 8 cases (72.7%). In the ICH group, most of the hemorrhage sites (77.8%) were located beneath the anastomosed area, and the mean hematoma volume was 16.98 ± 22.45 ml (range 3-57 ml). One case from the ICH group required hematoma evacuation. Among the adult patients (463 procedures [89.4%]), preoperative hypertension (p = 0.008), CT perfusion (CTP) stage > III (p = 0.013), and posterior circulation involvement (p = 0.022) were significantly associated with postoperative ICH. No significant differences between the postoperative ICH group and the no-hemorrhage group were detected in terms of postoperative neurofunctional status at discharge (p = 0.569) or at the last follow-up (p = 1.000). Neither was there a significant difference in future stroke risk (p = 0.538) between these two groups. Preoperative hypertension, CTP stage > III, and posterior circulation involvement are independent risk factors for postoperative ICH after direct or combined revascularization for MMD. After appropriate perioperative management, postoperative ICH has no significant correlations with the postoperative short-term and long-term neurofunctional status.

A case of moyamoya disease in a patient with multi-drug resistant tuberculosis

Moyamoya cerebral angiopathy is characterized by progressive stenosis or occlusion of the internal carotid artery or its branches with subsequent development of basilar collaterals. It is commonly seen in Asian population. Authors present a case report of a 12 year-old boy with Multidrug resistant tuberculosis with Moyamoya disease. Moyamoya disease rarely coexists with tuberculosis. However, we can infer that tuberculosis may coexist in a patient in a patient of Moyamoya disease.

Moyamoya disease with epileptic nystagmus: A case report

Epileptic nystagmus is a quick, repetitive, jerky movement of the eyeball caused by seizure activity, which is unaccompanied by other ictal phenomena. We report a case of moyamoya disease with epileptic nystagmus. A 23-year-old woman presented with a headache and transient hemiparesis on her left side. Magnetic resonance imaging showed no ischemic or hemorrhagic stroke lesions. Digital subtraction angiography confirmed stenosis of the terminal portion of the right internal carotid artery and the formation of moyamoya vessels on the right side. 123I-N-isopropyl-iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) showed decreased uptake in the right basal ganglia, frontal, and parietal regions. After electroencephalography (EEG) and a hyperventilation test were performed, nystagmus appeared and was accompanied with a declining level of consciousness. Ictal EEG during an attack showed no epileptiform discharge. Moreover, the patient sometimes experienced simultaneous upper limb-shaking and gelastic attacks. After superficial temporal artery to middle cerebral artery bypass surgery was performed on the right side, symptom frequency and duration gradually decreased. Decreased 123I-IMP SPECT blood flow in the right frontal region is considered a mechanism that causes the onset of epileptic nystagmus. It is presumed that the attack was caused by an ischemic abnormality in the saccade region of the frontal eye field. Moreover, revascularization can effectively treat the symptoms of moyamoya disease.

The application of hybrid operation suite in the management of cerebral and spinal vascular diseases and intracranial hypervascular tumors

Objective: To evaluate the effect of hybrid operation suite in the treatment of cerebral and spinal vascular diseases and intracranial hypervascular tumors. Methods: A retrospective study was conducted on 132 patients with various cerebral and spinal vascular diseases and intracranial hypervascular tumors who were treated by hybrid surgery at Department of Neurosurgery, Huashan Hospital from October 2016 to December 2017.There were 70 male and 62 female patients with a mean age of 48.33 years (range: 14-78 years), including 64 cases of intracranial aneurysm (41 complicated aneurysm cases), 28 cases of brain arteriovenous malformation (BAVM), 12 cases of hypervascular tumor, 12 cases of dural arteriovenous fistula (DAVF), 6 cases of carotid artery stenosis, 5 cases of Moyamoya disease, 3 cases of intracranial aneurysm or BAVM combined with tumor, 1 case of scalp arteriovenous fistula and 1 case of critical brain trauma in which a foreign metal stick approached the basal vascular circuit.Abnormalities were found in 16 cases in intraoperative angiography. The clinical data of all patients was collected as a perspective cohort. The success rate of hybrid surgery, intra-operative and post-operative complications, morbidity, mortality, rate of infection, the length of hospital stay were all analyzed to illustrate the effect of hybrid operation mode to traditional surgical pattern. Results: For 64 cases with intracranial aneurysms, the immediate complete occlusion rate was 90.5%, with a mortality of 4.7% and a morbidity of 14.0%. For 28 cases of BAVM and 12 cases of DAVF, all patients achieved total obliteration and favorable social independent outcomes after hybrid surgery, with no complication.For 6 cases of carotid artery stenosis and 5 cases of Moyamoya, intra-operative confirmed good cerebral reperfusion without any new post-operative neurologic deficits. After tumor vessels embolization, 4 out of 12 cases of hypervascular tumor needed intra-operative blood transfusion, and all patients achieved total tumor resection in a single stage. Only one patient with medulla oblongata hemangioblastoma died 6 months after operation due to respiratory deficit related pneumonia. Compared to traditional surgeries, the hybrid operation pattern did not significantly increase the total infection rate, central nervous system infection rate, hospital stay days and post-operative hospital stay days (all P>0.05) while the in-patient cost increased mildly (119 332 yuan vs.98 215 yuan, t=2.38, P=0.02). Conclusions: The operations of complex cerebral and spinal vascular diseases and intracranial hypervascular tumors can be performed in hybrid operation suite safely.This surgical mode can ensure the quality of operation and promote the development of innovative and complicated surgical procedures.

Characteristics of cognitive dysfunction in adult moyamoya disease: A single-center analysis

Objective To explore the characteristics and influencing factors of cognitive impairment in adult moyamoya disease (MMD). Methods A total of 466 adult patients with MMD (case group) admitted to Department of Neurosurgery, Huashan Hospital, Fudan University from June 2013 to December 2017 were retrospectively enrolled. The neuropsychological scale evaluation results were summarized. A matched group of 50 healthy adults were enrolled as the healthy control group. The characteristics of cognitive dysfunction were analyzed. Univariate and multivariate logistic regression were used to analyze the influencing factors of cognitive impairment in patients with MMD. Results Overall cognitive function, long-term memory, attention and executive function in the case group were significantly lower than those in the control group (all P 0.05). Conclusions According to the single-center experience of Huashan Hospital, Fudan University, cognitive dysfunction in adults with MMD involves specific cognitive domains and is affected by risk factors such as age, years of education and complications, while no significant difference in cognitive function has been found among different disease subtypes. Key words: Moyamoya disease; Adult; Cognition disorders; Factor analysis, statistical

Moyamoya disease: A retrospective study of 198 cases

BackgroundMoyamoya disease belongs to rare diseases which are arousing public awareness of its importance in China. In order to investigate the clinical features of inpatients diagnosed Moyamoya disease, the study was conducted to collect clinical information data of subjects on demographic information and clinical characteristics in Henan, China. MethodsThe data of 198 cases of Moyamoya disease from 56 tertiary hospitals in Henan province from January 2003 to June 2015 were collected retrospectively. Analysis was performed based on demographic, clinical and radiological characteristics of the patients. ResultsThe mean onset age was 44.03±14.45 years old. Unilateral limb weakness (36.4%) was the most common physical examination. Primary clinical manifestation was headache and dizziness (50.3%). Cranial CT showed cerebral infarction was mainly located in the frontal lobe (27.4%). MRA and DSA showed lesions mainly located in the middle cerebral artery (30.3% and 18.7%). ConclusionsClinical manifestations of Moyamoya disease varied. Early diagnosis was necessary to reduce the misdiagnosis rate of this disease. Symptoms, radiological characteristics, and lesion localization characteristics should be fully considered, especially for indicators with a certain onset age, headache and dizziness, lesion located in the frontal lobe of middle cerebral artery.

Intraoperative Anesthesiology Management and Patient Outcomes for Surgical Revascularization for Moyamoya Disease: A Review and Clinical Experience.

Moyamoya disease (MMD) is a rare cerebrovascular condition, often presenting as a headache or stroke in adults. Anesthetic management of this illness may challenge providers because it can affect the long-term neurologic outcome and hospital length of stay (LOS) in patients with MMD. A literature search was conducted to assess etiology and epidemiology, as well as existing reports of intraoperative management of MMD. Due to sparse findings, the search was expanded to include studies of the use of intraoperative anesthetic agents during other neurosurgical procedures. We also retrospectively reviewed all MMD cases from January 1, 2009, to December 31, 2015, at Memorial Hermann Hospital-Texas Medical Center, where intraoperative management involved craniotomy and surgical revascularization. Data were collected primarily on the use of several anesthetic agents. The LOS and any adverse events were also recorded for each case. The data were divided into two equivalent case cohorts: (1) January 1, 2009, to February 18, 2013, and (2) February 19, 2013, to December 31, 2015. Remifentanil use notably increased between the first and second time periods while fentanyl use decreased. Desflurane usage also demonstrated an observed increase when our two cohorts were compared. Additionally, there was a decrease in the mean LOS between the first and second periods of 3.9 and 3.3 days, respectively. Increasing use of remifentanil in MMD cases could be attributed to its ability to provide more stable hemodynamics during induction, maintenance, and emergence of anesthesia when compared with fentanyl. Lower systolic pressures, diastolic pressures, and heart rates were reported in patients receiving remifentanil over fentanyl.

Abstract TMP101: Relationship Between RNF213 p.R4810K (c.14429G&gt;A) Variant and Anatomical Variations of the Circle of Willis

Background and purpose: RING finger protein 213 ( RNF213 ) gene is strongly associated with intracranial arterial stenosis as well as Moyamoya disease and its dysregulation is known to impair cerebral perfusion in rodents. We thus investigated the relationship between RNF213 p.R4810K (c.14429G&gt;A) variant and the anatomical variations of the circle of Willis in cerebrovascular disease. Methods: We consecutively enrolled non-cardioembolic stroke or transient ischemic attack patients with (n = 20) or without (n = 80) RNF213 p.R4810K (c.14429G&gt;A) variation from those who participated in the biobank of our Institute over the past 2 years. Moyamoya disease cases were excluded. We evaluated anatomical variations of the vessels constituting the circle of the Willis, namely, intracranial internal carotid artery, anterior communicating artery (AcomA), anterior cerebral artery A1 segment, posterior communicating artery (PcomA), posterior cerebral artery P1 segment, and middle cerebral artery M1 segment, using maximum intensity projection of a time-of-flight magnetic resonance angiography collected at 3 Tesla. Results: The RNF213 p.R4810K (c.14429G&gt;A) variant carrier had higher frequency of focal narrowing of the M1 segment compared to the non-carrier (50% vs 10%, p&lt;0.01) and an absence of AcomA (15% vs 3.7%, p=0.09). By contrast, unexpectedly, unilateral or bilateral absence of PcomA was significantly less frequent (25% vs 61%, p&lt;0.01). Multivariate analysis adjusted for age and sex showed that the variant carrier state was independently associated with unilateral or bilateral presence of PcomA (odds ratio (OR) 4.44, 95% confidence interval (CI) 1.01 - 20.6, p&lt;0.05) and focal M1 narrowing (OR 3.30, 95% CI 0.82 - 12.6, p=0.09). Conclusions: The RNF 213 p.R4810K (c.14429G&gt;A) variant carrier showed higher frequency of arteriopathy in the anterior circulation accompanied by higher patency rate of PcomA. In the variant carrier, dysplasia of the anterior circulation arteries may lead to compensatory collateral flow from posterior to anterior circulation through PcomA.

Association of CD40 SNPs with Moyamoya in a Chinese children population

Background: The etiology of Moyamoya disease (MMD) remains unknown to a large extent. Immune and inflammation dysfunction may play a role in the pathogenesis of this rare disease. Coexisting Kawasaki disease (KD) with MMD were reported and both diseases have a feature of vasculopathy, raising the hypothesis that there may be some common pathologic factors. We investigated single nucleotide polymorphisms (SNPs) previously identified in KD and performed a genetic analysis among Chinese pediatric patients with MMD.Results: We analyzed patients’ DNA for the SNPs in B lymphoid tyrosine kinase, CD40, and coatomer protein complex beta-2 subunit, which had been associated with KD by literatures. Genotyping was performed by sequencing the genetic regions containing the SNPs with customized primers. A total of 5 genotype polymorphisms were examined among 48 pediatric MMD cases and 50 healthy controls. The mean age of MMD children was 6.72 ± 3.63 years old, while 7.31 ± 3.79 in controls. We found two SNPs of CD40 were associated with MMD. Polymorphisms rs4813003 major allele CC and rs1535045 minor allele TT were significantly higher in MMD cases. The other SNPs showed no statistical difference between MMD cases and controls.Conclusions: Our findings provide evidence that there may be a relationship between MMD and auto-immune dysfunction. We hypothesize that these genetic features may lead to the pathogenesis within the vascular wall. Further study regarding whether CD40 can function as the personalized target of MMD should be investigated in future.

Circular RNAs and neutrophils: Key factors in tackling asymptomatic moyamoya disease.

Moyamoya disease (MMD) represents a rare steno-occlusive disorder affecting the terminal ends of the internal carotid artery and promoting the development of a poor, abnormal vascular network at the brain's base. Primarily affecting East Asian countries over Western populations, MMD can be further divided into symptomatic and asymptomatic subtypes. The current knowledge of the underlying mechanisms and potential management strategies for asymptomatic cases of MMD are largely lacking and thus warrant investigation to elucidate the pathology of this rare disorder. Here, we assess research examining the expression profile of circular RNAs (circRNAs) of neutrophil transcriptome in asymptomatic MMD patients. These findings conclude that 123 differentially expressed circRNAs significantly contributed to metabolism, angiogenesis, and immune response. The hypoxia-inducing factor-1α signaling pathway was also revealed to be crucial in angiogenesis. We also evaluate current therapeutic options demonstrating the potential for MMD patients, such as EC-IC bypass and ischemic pre- and post-conditioning. These approaches combined with recent findings on the circRNA expression profile suggest a crucial role of anti-inflammatory and angiogenic-related mechanisms underlying MMD. Investigating the role of circRNAs and neutrophils in the asymptomatic MMD subtype may provide insight into its elusive pathology and direct future approaches to combat the progression of this rare disease.

Atherosclerosis or nonatherosclerotic vasculopathy? Moyamoya disease in a mid-aged adult

All causes of cerebrovascular disease should be considered in any patient presenting with ischemic stroke, despite the patient have concomitant risk factors for atherosclerosis. Here, we reported a case of Moyamoya disease (MMD) at a rather old age and with the presence of multiple risk factors for atherosclerosis. It is difficult to consider MMD at first glance, and it is easy to choose the wrong treatment in the first place. The key radiological feature for differentiation is the bilateral intracranial stenosis, rather than atherosclerotic changes, which are characterized as plaques with an uneven surface.